Associations of biomechanical properties of the cornea with environmental and metabolic factors in an elderly population : the ALIENOR study

PURPOSE: The purpose of this study was to assess the associations of biomechanical properties of the cornea with metabolic and environmental factors in an elderly population. METHODS: The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition, and Maladies OculaiRes) study is a population-based study. In 2009-2010, 624 subjects, aged 74 years or more, underwent an eye examination, including intraocular pressure (IOP), central corneal thickness (CCT), and biomechanical properties of the cornea measurements using the Ocular Response Analyzer. Socio-demographic, lifestyle, and medical history data were collected using standardized questionnaires. Mean lifetime ambient ultraviolet (UV) exposure was estimated using residential history and statistics of UV radiation at each location using the Eurosun UV database. RESULTS: Mean age was 82.2 ± 4.3 years. Mean corneal hysteresis (CH), corneal resistance factor (CRF), and CCT were 9.4 ± 1.9, 9.8 ± 1.9 mm Hg, and 551.6 ± 36.8 μm, respectively. In the multivariate analysis, CH and CRF values were significantly lower in subjects older than 80 years (-0.56; 95% confidence interval [CI]: -0.89;-0.24); P < 0.001 and -0.48; 95% CI: -0.75;-0.20; P < 0.001, respectively), in subjects having higher ambient UV exposure (-0.50; 95% CI: -0.88;-0.12; P < 0.01; and -0.46; 95% CI: -0.78;-0.13); P < 0.05, respectively), and in subjects with high plasma LDL cholesterol (CH: -0.46; 95% CI: -0.86;-0.03; P < 0.05; and CRF: -0.37; 95% CI: -0.72;-0.008; P < 0.05). Central corneal thickness was significantly higher in former smokers than in never smokers (+11.01; 95% CI: 0.48;21.55; P < 0.05) and was not significantly associated with age, ambient UV exposure, diabetes, or LDL cholesterol. CONCLUSIONS: Biomechanical properties of the cornea are modified by metabolic and lifetime environmental factors, especially UV exposure. The manner these factors may influence onset and progression of ocular diseases or IOP measurements need further investigation

Mediterranean Diet Adherence and Risk of Depressive Symptomatology in a French Population-Based Cohort of Older Adults

Several foods from the Mediterranean Diet (MeDi) have already been characterized as beneficial for depression risk, while studies focusing on adherence to the overall MeDi are lacking among older adults at higher risk of depression. The aim of this study was to assess the association between MeDi adherence and the risk of depressive symptomatology (DS) in an older French cohort followed for 15 years. Participants from the Three-City Bordeaux cohort answered a food frequency questionnaire used to assess their MeDi adherence. The Center for Epidemiologic Studies Depression (CES-D) scale score of 16 or greater and/or use of antidepressant treatment ascertained at each visit defined incident DS. Random-effect logistic regression models were adjusted for potential confounders. Among 1018 participants, aged 75.6 years (SD 4.8 years) on average at baseline, 400 incident cases of DS were identified during the follow-up. Only when restricting the definition of DS to a CES-D score ≥ 16 was a borderline-significant trend towards a benefit of greater adherence to the MeDi with reduced odds of DS found (p-value = 0.053). In this large sample of older French adults, a potential benefit of greater adherence to the MeDi regarding the risk of DS would depend on the definition of DS

Invest Ophthalmol Vis Sci

Purpose: To analyze the association between skin autofluorescence (sAF), estimating tissue accumulation of advanced glycation end-products (AGEs), and open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants, Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on-going epidemiologic population-based study on age-related eye diseases. In 2009 to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects underwent a complete eye examination, including optic disc color photography and spectral-domain optical coherence tomography (SD-OCT) examination. Sociodemographic and medical history data were collected using standardized questionnaires. Glaucoma diagnosis was made using optic nerve head retinophotography and International Society for Epidemiologic and Geographical Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3 years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU), respectively. In a multivariate analysis, higher sAF values (>/=2.7 AU) were associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03; 5.04). Other variables significantly associated with OAG were age (OR = 1.10, 95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >/=20 pack-years [OR = 3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a long-term biomarker of metabolic memory, and smoking are independently associated with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of oxidative stress, could play a role in the pathogenesis of glaucomatous chronic optic neuropathy

Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41-0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39-0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E-3) Consortium

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans

Ophthalmology

PURPOSE: To investigate associations of adherence to the Mediterranean diet (MeDi) with incidence of advanced age-related macular degeneration (AMD; the symptomatic form of AMD) in 2 European population-based prospective cohorts. DESIGN: Prospective cohort study of the Rotterdam Study I (RS-I) and the Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study populations. PARTICIPANTS: Four thousand four hundred forty-six participants 55 years of age or older from the RS-I (The Netherlands) and 550 French adults 73 years of age or older from the Alienor Study with complete ophthalmologic and dietary data were included in the present study. METHODS: Examinations were performed approximately every 5 years over a 21-year period (1990-2011) in RS-I and every 2 years over a 4-year period (2006-2012) in the Alienor Study. Adherence to the MeDi was evaluated using a 9-component score based on intake of vegetables, fruits, legumes, cereals, fish, meat, dairy products, alcohol, and the monounsaturated-to-saturated fatty acids ratio. Associations of incidence of AMD with MeDi were estimated using multivariate Cox proportional hazard models. MAIN OUTCOMES MEASURES: Incidence of advanced AMD based on retinal fundus photographs. RESULTS: Among the 4996 included participants, 155 demonstrated advanced incident AMD (117 from the RS-I and 38 from the Alienor Study). The mean follow-up time was 9.9 years (range, 0.6-21.7 years) in the RS-I and 4.1 years (range, 2.5-5.0 years) in the Alienor Study. Pooling data for both the RS-I and Alienor Study, participants with a high (range, 6-9) MeDi score showed a significantly reduced risk for incident advanced AMD compared with participants with a low (range, 0-3) MeDi score in the fully adjusted Cox model (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P = 0.04 for trend). CONCLUSIONS: Pooling data from the RS-I and Alienor Study, higher adherence to the MeDi was associated with a 41% reduced risk of incident advanced AMD. These findings support the role of a diet rich in healthful nutrient-rich foods such as fruits, vegetables, legumes, and fish in the prevention of AMD

Ophthalmology

PURPOSE: Age-related macular degeneration(AMD) is a common multifactorial disease in elderly with a prominent genetic basis. Many risk variants have been identified, but the interpretation is still challenging. We investigated the genetic distribution of AMD-associated risk variants in a large European consortium, calculated attributable, and pathway-specific genetic risks, and assessed the influence of lifestyle on genetic outcomes. DESIGN: Pooled analysis of cross-sectional data from the E3 consortium. PARTICIPANTS: 17.174 individuals aged 45+ participating in 6 population-based cohort studies, 2 clinic based studies, 1 case-control study. METHODS: AMD was diagnosed and graded based on fundus photographs. Data on genetics, lifestyle, and diet were harmonized and completed where necessary. Minor allele frequencies and population attributable fraction (PAF) were calculated per single nucleotide polymorphism (SNP). A total genetic risk score (GRS) and pathway-specific risk scores (complement, lipid, extra-cellular matrix, other) were constructed based on the dosage of SNPs and conditional beta's; a lifestyle score was constructed based on smoking and dietary intake. RESULTS: The risk variants with the largest difference between late AMD cases and controls, and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109). Both risk increasing and protective variants had the highest PAFs. Combining all genetic variants, the total genetic risk score ranged from -3.50 to 4.63, was normally distributed and increased with AMD severity. Of the late AMD cases, 1581/1777 (89%) had a positive total GRS. The complement pathway and ARMS2 were by far the most prominent genetic pathways contributing to late AMD (positive GRS 90% of late cases), but risk in three pathways was most frequent (35% of late cases). Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD at least twofold. CONCLUSIONS: Genetic risk variants contribute to late AMD in the majority of cases. However, lifestyle factors have a strong influence on the outcome of genetic risk, and should be a strong focus in patient management. Genetic risks in ARMS2 and the complement pathway are present in the majority of late AMD, but are mostly combined with risks in other pathways

Cardiovasc Diabetol

BACKGROUND: Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up. METHODS: During year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016. RESULTS: The participants were mainly men (59.5%), 51.5 +/- 16.7 years old, with BMI 25.0 +/- 4.1 kg/m(2), diabetes duration 21.5 +/- 13.6 years, HbA1C 7.6 +/- 1.1%. LDL cholesterol was 1.04 +/- 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 +/- 26.6 ml/min/1.73 m(2). Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (>/= 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 +/- 0.73 arbitrary units (AU) vs 2.08 +/- 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30-13.07]; p = 0.02 for 1 AU of SAF) and Kaplan-Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001). CONCLUSION: A high SAF predicts MACE in patients with T1D

Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia